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Tumor Immunology
Jason Cyster[1]
Malignancy of germinal center B cells is a frequent cause of lymphoma. We have characterized a novel tumor
suppressor pathway involving S1PR2, Ga13 and ArhGEF1, that is frequently disrupted in germinal center B cellderived lymphoma. We are studying how disruption of this pathway contributes to growth and dispersal of
lymphoma cells. Our studies on immune cell migration also have direct relevance to understanding how we can
better equip effector lymphocytes to attack tumors.
Other Research in Dr. Cyster's Lab:
Diabetes and Autoimmunity[2] ?Development and Differentiation[3] ?Immune Regulation[4] ?
Immune Response to Microbial Pathogenesis [5]
Larry Fong
Our program is focused upon defining the immune response to tumor antigens in order to develop
potential vaccine and immunotherapeutic strategies. Currently, our research program is divided into
three distinct but interrelated areas of interest. These include studying dendritic cell biology, exploring
approaches to break tolerance against self-antigens, and characterizing effector and memory T cells
following tumor immunotherapy.
Dendritic cell function
Dendritic cells (DC) are known to be comprised of multiple subsets (e.g. myeloid DC, plasmacytoid
DC), each of which may have distinct functions. By studying different DC subsets in the context of
malignancy, we hope to develop approaches to use DC as a means of inducing therapeutic antitumor
immunity in vivo in both animal models and cancer patients.
Tolerance to tumor associated antigens
The majority of the current tumor-associated antigens represent self-antigens that are either aberrantly
or overly expressed by the malignancy. As a result, the vast majority of solid tumors are not
immunogenic. We are using mouse and human models to define the antigen specificity of anti-tumor
immune responses that either occur spontaneously or are induced with immunotherapy.
Evaluating antigen-specific T cell responses
We have demonstrated that in vivo expansion of CD8 T cells identified with MHC/peptide tetramers
can correlate with tumor responses in cancer patients. Current efforts underway are to characterize the
T cell response following vaccination against tumor associated (self) antigens utilizing novel assays
that couple tetramer staining (antigen-specificity) with T cell function. Moreover, we are currently
characterizing the immune response not only within the blood, but also within the tissues and tumors in
order to examine the distribution of an immune response. By identifying the dynamics of antigen
specific T cells and their capacity to develop immunologic memory, we hope to develop improved
strategies in tumor immunotherapy.
Matthew Krummel[6]
The lab is currently using advanced imaging to visualize T cell activation in tumor draining lymph
nodes and effector sites. We are generating two models?one for breast cancer and one for melanoma?in
which the tumors are fluorescent. Interactions between tumors and T lymphocytes are revealed uing
fluorescent dyes, including GFP fusions.
Other Research in Dr. Krummel's Lab:
Autoimmunity [2]?Immune Regulation[4] ?Immune Receptors and Signaling [7]
Lewis Lanier [8]
NK cells have the ability to recognize and kill transformed cells without prior immunization (Lanier,
Nat. Med. 2001[9]). The NKG2D receptor expressed on NK cells and CD8+ T cells recognizes a family
of MHC class I-related proteins, which includes in humans the MICA, MICB, and ULBP proteins and
in mice the RAE-1, H60 and MUTL1 proteins. (Cerwenka et al., Immunity. 2000[10]). These NKG2D
ligands are generally not expressed on normal, health tissues in adults; however, they are frequently
over-expressed by many types of tumors. Expression of NKG2D ligands on tumors can initiate NK cell
activation and result in tumor rejection (Cerwenka et al., Proc Natl Acad Sci. 2001[11]). Current studies
in our lab focus on the NKG2D ligands, as well as other NK receptors that have been implicated in antitumor immunity.
Other Research in Dr. Lanier's Lab:
HIV and Viral Immunity[12] ?Diabetes and Autoimmunity[2] ?Immune Receptors and Signaling[7]
Will Seaman[13]
Our laboratory is interested in the receptors that activate or inactivate natural killer (NK) cells, which
spontaneously kill tumors.
Other Research in Dr. Seaman's Lab:
Allergy and Asthma[14] ?Immune Receptors and Signaling[7] ?Immune Response to Microbial
Pathogenesis[5]
Matthias Wabl[15]
The genes that are necessary for normal, controlled cell growth are called tumor suppressor genes, and
inactivation of these genes can lead to tumor formation. The majority of known tumor suppressors were
located by the genetic mapping of organisms with an inherited predisposition for cancer. However,
familial predisposition to cancer is responsible for only approximately 10% of human cancers and
identification of tumor suppressors involved in non-familial cancers has been slower. The goal in the
lab is to define the set of tumor suppressors that when deleted contribute to the formation of
lymphocyte tumors in mice; and their interactions with protooncogenes, as completely as possible.
We define cancer genes by retroviral insertional mutagenesis, combined with chemical mutagenesis, to
inactivate both alleles in cells of a given mouse. The offspring of chemically mutagenized male mice
are subjected to insertional mutagenesis by retrovirus that induces tumors of lymphocyte origin. The
viral genome disrupts potential suppressor genes, leading to their inactivation, and at the same time
creates a marker for identifying the insertion loci. The tagged cancer genes are cloned and sequenced.
In collaboration with several other labs, we characterize a subset of the cancer genes and determine the
nature of their cooperation with other oncogenes (co-mutations).
Other Research in Dr. Wabl's Lab:
Development and Differentiation[3] ?Immune Receptors and Signaling[7] ?Inflammation[16]
Zena Werb [17]
It is now widely recognized that the inflammatory microenvironment of mutated tumor cells is a major
determinant of malignancy in cancers. The host response to tumorigenesis includes the recruitment of
innate and acquired immune cells. Cells of the myeloid lineage, such as macrophages, neutrophils,
mast cells, and myeloid suppressor cells are major components of the complex microenvironment of
neoplastic cells in solid tumors. We are using transgenic mouse models of breast cancer and intravital
microscopy to investigate the mechanisms by which inflammatory and immune cells enhance
mammary tumor development by regulating angiogenesis, tumor growth, tumor dissemination and
metastasis and by suppressing the anti-tumor immune response. We are also studying how tumor cells
recruit the immune cells to the tumor and metastatic sites.
Other Research in Dr. Werb's Lab:
Inflammation [16] ? Development and Differentiation [3]
Contact Us
UCSF Main Site
© 2014 The Regents of the University of California
Source URL: http://immunology.ucsf.edu/tumor_immunology
Links:
[1] http://profiles.ucsf.edu/jason.cyster
[2] http://immunology.ucsf.edu/diabetes-and-autoimmunity
[3] http://immunology.ucsf.edu/dev_differentiation
[4] http://immunology.ucsf.edu/regulation
[5] http://immunology.ucsf.edu/immune_response-to_mp
[6] http://profiles.ucsf.edu/max.krummel
[7] http://immunology.ucsf.edu/receptors
[8] http://profiles.ucsf.edu/lewis.lanier
[9] http://www.nature.com/nm/journal/v7/n11/full/nm1101-1178.html
[10] http://www.sciencedirect.com/science/article/pii/S1074761300802228
[11] http://www.pnas.org/content/98/20/11521.long
[12] http://immunology.ucsf.edu/hiv-and-viral-immunity
[13] http://profiles.ucsf.edu/william.seaman
[14] http://immunology.ucsf.edu/allergy-and-asthma
[15] http://profiles.ucsf.edu/matthias.wabl
[16] http://immunology.ucsf.edu/inflammation
[17] http://profiles.ucsf.edu/zena.werb